The concept of making inexpensive microfluidic channels on paper and other woven and non-woven fibrous and porous surfaces has been successfully proven. The aim of building such systems has been to fabricate low-cost bio-analytical and indicator devices, with direct envisaged applications in detecting waterborne bacteria and metals ions in drinking water, the presence of some specific proteins or biomarkers in body fluid (cancer test), the level of glucose and other bio-chemical substances in human or animal blood and urine samples. Developments of low-cost paper-based bio-analytical and environmental analytical devices have so far allowed quick and single step reaction to detect analytes in a fluid sample.
Researchers in Harvard University led by Whitesides (see Martinez, A. W., Phillips, S. T., Butte, M. J. and Whitesides G. M., and “Patterned Paper as a platform for Inexpensive, Low-Volume, Portable Bioassays”, Angew. Chem. Int. Ed. 46, 1318-1320 (2007)) have recently created channels on paper by printing patterns of conventional photoresists polymers (PMMA). Paper provides the capillary channels, while the photoresist polymers form the barrier which defines the channel. More recently, the Harvard group further developed their photoresist technique in making fine channels in paper. They used an ink jet printer to print patterns on transparent polymer films, which were used as masks for photo lithography to generate photoresist patterns in paper following their published approach (Martinez, A. W., Phillips, S. T., Wiley, B. J., Gupta, M. and Whitesides, G. M. Lab on a Chip, (2008) DOI: 10.1039/b811135a). They showed that fine microfluidic channels can be generated in paper using the photoresist barrier approach and these channels have comparable resolution to the microfluidic channels made using other substrates such as silicon wafer. A problem associated with the use of such photolithography techniques is that they result in rigid and brittle barriers which can be easily damaged if the paper is creased or crumpled.
In another published paper, the Harvard group used an x-y plotter to draw channels on paper surface (see Bruzewicz, D. A., Reches, M. and Whitesides, G. M., “Low-Cost Printing of Poly(dimethylsiloxane) Barriers to Define Microchannels in Paper”, Anal Chem. 80, 3387-3392 (2008)). The plotter's pens were filled with a hydrophobic solution of polydimethyl siloxane (PDMS) in hexane, and a plethora of patterns several centimeters long with channel 1 cm to 2 mm wide were created. Their second micro-channels system created on paper surface overcame a major drawback of the first one, ie the rigid and brittle barrier material of conventional photoresist polymers. Their second system, however, has a poor channel resolution and definition, since the penetration of PDMS solution in paper sheet cannot be controlled. The use of silicones to define the walls of the microchannels would also require FDA approval in view of the potential health related issues. Both fabrication approaches result in physical barriers which define the periphery of the micro-channels.
Abe et al. (Abe, K; Suzuki, K; Citterio, D. “Inkjet-printed microfluidic multianalyte chemical sensing paper”, Anal. Chem. (2008) 6928-6934) presented a method of using a solution of hydrophobic polymer (PS) to impregnate paper. After the polymer physically covered the fibre surface and dried, they used a Microdrop dispensing device to deliver solvent droplets to dissolve the polymer from the fibre surface, thus forming microfluidic channels by restoring the hydrophilicity of the paper. These authors also used the Microdrop dispensing device to deliver chemical sensing agents into their pattern to form a functional device for biomedical detection.
In U.S. Pat. No. 7,125,639, Molecular Transfer lithography, the inventor Charles Daniel Schaper (class 430/253, 430/258) describes a process for patterning a substrate comprising the steps of: 1) coating a carrier with a photosensitive material, 2) exposing the photosensitive material to a pattern of radiation, and 3) physically transferring the exposed material to the substrate.
In U.S. Pat. No. 6,518,168, Self-assembled monolayers direct patterning of surfaces, by Paul G Clem et al (filing date Nov. 2, 1998), A technique for creating patterns of material deposited on a surface involves forming a self-assembled monolayer in a pattern on the surface and depositing, via chemical vapor deposition or via sol-gel processing, a material on the surface in a pattern complementary to the self-assembled monolayer pattern. The material can be a metal, metal oxide, or the like.
In WO/2008/060449 MICROFLUIDIC DETECTOR, by BUTTE, Manish, J. et al (Application date Sep. 11, 2007), articles and methods for determining an analyte indicative of a disease condition are provided. In some embodiments, articles and methods described herein can be used for determining a presence, qualitatively or quantitatively, of a component, such as a particular type of cell, in a fluid sample. In one particular embodiment, a low-cost microfluidic system for rapid detection of T cells is provided. The microfluidic system may use immobilized antibodies and adhesion molecules in a channel to capture T cells from a fluid sample such as a small volume of blood. The captured T cells may be labelled with a metal colloid (eg, gold nanoparticles) using an antibody specific for the T Cell Receptor (TCR), and metallic silver can be catalytically precipitated onto the cells. The number of T cells captured can be counted and may indicate a disease condition of a patient such as severe combined immune deficiency or human immunodeficiency virus.
Those patent applications and research papers proposed methods to make microfluidic systems and devices using a variety of materials, including using paper and other non-woven or porous materials as substrates. Microfluidic channels can be fabricated using paper and other non-woven or porous materials in batch operations. However all of the above-noted systems utilise complex and time consuming processes that cannot be readily adapted to allow for low cost, high speed industrial production. Furthermore, all these earlier systems rely on a physical barrier to define the microfluidic channels.
It is an object of the present invention to provide a method of fabricating a microfluidic system which overcomes at least one of the disadvantages of prior art methods.